An Introduction
Zika virus has fast become one of the most talked about threats to developmental health worldwide. While it tends to have very minor symptoms for adults, fetal exposure to zika virus has been confirmed to cause damage to the brain.
Since our last update the relationship between zika virus and the increased incidence of microcephaly in South America has been strengthened. We are starting to develop a picture of how zika virus may have this effect on the developing fetus.
Transmission of Zika Virus
Zika is primarily spread by female aedes aegypti mosquitoes that have been infected with the virus through drinking infected blood. Once infected the mosquito's saliva transmits the virus to the next person. While zika virus has been found in most bodily fluids (including semen, blood, saliva, and breastmilk) cases of transmission from person to person are still rare. The incubation period of the virus is between 3 and twelve days, after which point it appears that it can no longer be transmitted.
Vertical transmission of zika virus, the transmission of the virus from mother to fetus, has been demonstrated in laboratory mice and has been confirmed in humans via post-natal blood tests and autopsies.
How Does Zika Affect the Developing Brain?
During its first stages of growth the brain is made of neural stem cells, these are cells which can develop into any kind of brain cell. All of your brain cells start as neural stem cells. For reasons we have yet to determine, neural stem cells are preferentially infected by zika virus. When zika was applied to cells grown in a lab the virus was able to infect more than 85% of neural stem cells after 3 days, compared to less than 10% of fetal kidney cells.
Once the neural stem cell is infected its internal machinery is hijacked by the virus so that the virus can reproduce. This has two main effects that we know of: first, it stops the cell from being able to divide so the brain has fewer overall cells; secondly, it triggers a receptor called TLR3 which causes a kind of immune response within the cell. Cells which have a high expression of TLR3 stop growing and are ultimately killed.
The combination of cell death and halted division results in a shrinking of the brain. There is some evidence that this shrinking effect can be minimised by administering a TLR3 blocker, but it is unclear what effect this would have on the fetus as a whole.
When Is It Most Dangerous?
There is no evidence to suggest that being infected with zika virus will negatively impact pregnancies that occur later in life. The main concern is the contraction of zika virus during pregnancy. The first and second trimester appear to be the points with the highest chance of harm for the fetus.
A survey of Brazilian mothers of children with microcephaly showed that 60% had experienced symptoms of zika in their first trimester, 14% in their second trimester, while 26% had experienced no symptoms at all. None of the women had experienced symptoms of zika in their third trimester.
A mouse model of zika virus infection demonstrated that the virus is transmitted from the mother to the placenta, and then from the placenta to the fetus. The placenta appears to act a host for the virus, housing it at a concentration 1000 times greater than is found in the mother's bloodstream. The virus is likely able to get into the placenta via cells called extravillous trophoblasts which make up a high proportion of the placenta is the first and second trimesters but are much less dense during the third trimester. This may reduce the likelihood of zika transmission in the third trimester.
Where Do We Go From Here?
The more time passes the closer we come to understanding how zika virus has this effect on the developing brain, and how we can stop it. The World Health Organisation advises that women who are pregnant avoid zika infected areas as much as possible, and avoid fluid exchange with individuals who may be infected. The risk of microcephaly has risen dramatically in Brazil since the zika outbreak began, but with researchers the world over searching for answers we're hopeful that numbers will soon begin to decline.